Researchers at the Cleveland Clinic have identified a significant link between bacteria residing in tumors and the effectiveness of immunotherapy in treating head and neck squamous cell carcinoma. Two studies published in Nature Cancer reveal that higher levels of bacteria in the tumor microenvironment can suppress immune responses, contributing to treatment resistance.
In a statement, Timothy Chan, M.D., Ph.D., chair of the Department of Cancer Sciences and lead author of one of the studies, emphasized the importance of this research. “These studies shift the focus of immunotherapy resistance research beyond tumor genetics to unexpected factors like the tumor microbiome,” he said. “By identifying bacteria as a key barrier to treatment, we’re opening the door to new strategies for patient selection and targeted antibiotic therapies.
Study Findings and Implications
The research team, which included Daniel McGrail, Ph.D., and Natalie Silver, M.D., M.S., validated their findings using patient samples, preclinical models, and clinical trial data. In the first paper, Dr. McGrail analyzed genetic data from tumor samples, discovering that increased bacterial levels—not specific strains—diminished immune responses.
Dr. Silver further confirmed these findings through preclinical models, where the use of antibiotics reduced tumor size and enhanced immune response. Conversely, adding bacteria made tumors more resistant to immunotherapy. Collaborating with Renata Ferrarotto, M.D., from the University of Texas MD Anderson Cancer Center, the team examined clinical trial samples to understand how bacterial presence affects treatment outcomes.
Dr. Silver noted, “Immunotherapy is a promising treatment option for patients with head and neck cancer, but the majority unfortunately do not respond. Our research examines how bacteria influence treatment failure, which can help us identify patients most likely to benefit from immunotherapy.”
Clinical Trial Analysis and Future Research
The second study, led by Dr. Chan, involved a data analysis of the Javelin HN100 Phase III clinical trial, which assessed whether adding anti-PDL1 immunotherapy to standard chemoradiotherapy would improve patient outcomes. The analysis determined that patients with elevated tumor bacteria levels experienced poorer outcomes with immunotherapy compared to those receiving standard treatment.
These two studies indicate that high bacterial levels in tumors attract neutrophils, white blood cells that typically combat infections. While essential for fighting bacterial threats, neutrophils can hinder the immune system’s ability to respond effectively to cancer treatments. This insight provides a foundation for further exploration into the reasons behind bacterial attraction to tumors and potential modifications to improve treatment efficacy.
In light of these findings, Dr. Silver has initiated a clinical trial to investigate whether antibiotics can reduce bacterial levels in tumors and enhance immunotherapy responses in patients with head and neck squamous cell carcinoma. Concurrently, Dr. McGrail is researching the influence of bacteria on cancer development, aiming to devise new therapeutic strategies. Dr. Chan is exploring the possibility that bacteria may induce DNA mutations within tumors.
Dr. McGrail remarked, “By uncovering the tumor microbiome’s role in immunotherapy resistance, these studies mark a significant step forward in understanding the complex interactions between cancer and the immune system.” This research broadens the perspective on cancer treatment and paves the way for developing personalized therapies that could improve patient outcomes.
